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Rheumatoid Arthritis (RA)

Contributor: Jessica Berman, MD

Case 1

A 20 year old female comes to see you because 4 months ago she began having pain and stiffness in the MCPs and wrists. The symptoms are worse in the morning lasting for 1 hour and improve with movement. There is fatigue but no other problems identified on review of systems. On exam the wrists are slightly swollen and tender and MCPs are tender but not swollen. ESR is 48. The rheumatoid factor (RF) is positive at 105 and the anti-cyclic citrullinated peptide (anti-CCP or ACPA) is >250. X-rays show osteopenia but no erosions.

What is the significance of the tests ordered in making the diagnosis of RA?

  • Antibodies commonly checked when RA is suspected include rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody. Presence of these antibodies is predictive of more aggressive disease and may prompt more aggressive treatment. Anti-CCP is more specific for RA than RF. It is important to remember that RA is a clinical diagnosis and that antibody positivity is not necessary in order to make a diagnosis, however. This is called "seronegative RA". The 2010 Classification criteria for RA are used to enroll patients in clinical trials and caution should be used when approaching patients in clinical practice.
  • Rheumatoid arthritis is a chronic, progressive inflammatory disease affecting primarily the small joints of the hands, feet, wrists and ankles in a symmetric fashion and characterized by the presence of erosions on radiographs. The presence of erosions on x-ray is pathognomonic for the diagnosis of RA. It is said that up to 80% of patients with RA will have erosions within the first 3 months of the illness. However, early on in the disease they are not always present and soft tissue swelling only may be the only manifestation.
  • Although the ESR is often elevated in patients with RA, especially with active polyarthritis, patients can have signs of active inflammation and a normal ESR. A high ESR is a marker for systemic inflammation and is probably indicative of an overall worse prognosis.

What are the typical features seen in this patient that are helpful in making the diagnosis of RA?

  • This patient clinically has diffuse MCP and wrist synovitis which is indicative of RA. It is important to remember that RA is a clinical diagnosis. Other findings which support the diagnosis include the presence of osteopenia on x-ray and the high ESR. Since anti-CCP is highly specific for the disease it adds to the weight of the diagnosis. The presence of RF and anti-CCP put this patient at high risk for progression and should be considered when making treatment decisions.

Case 2

A 58-year old woman was diagnosed with RA 15 years ago when she first presented with 16 tender and 12 swollen joints including the MCPs, PIPs, and wrists. At that time she was treated with hydroxychloroquine, sulfasalazine, and methotrexate without improvement. Past medical history is notable for HTN and a smoking history of 1ppd x 10 years.

On exam today, the patient shows the typical signs of RA with bilateral flexion deformities of the fingers and ulnar drift at the wrists. There is evidence of active synovitis in the left 2nd MCP only.

The following labs are obtained: ESR is 6 mm/hr, RF is positive at 105 and CCP is positive at >250. X-rays show multiple erosions in the MCPs and the wrists. The patient is currently on prednisone 15mg daily, methotrexate 20mg weekly and etanercept 50mg weekly. The etanercept was just added 6 months ago. The patient continues to have AM stiffness lasting longer than 2 hours and is unable to perform ADLs. The option for other treatments is discussed.

What are infection risks for this patient given the current therapy?

  • Etanercept blocks tumor necrosis factor (TNF) and is immunosuppressive, putting patients who take it at higher risk for infections. In particular, the risk for skin and respiratory infections is known to be greater in patients using this therapy. Because this therapy blocks the formation of granulomas, a process important in containing tuberculosis, documenting that a patient is negative for tuberculosis exposure prior to starting therapy is mandatory.
  • RA patients should be monitored closely for the signs and symptoms of infection and should receive immunizations for influenza and pneumococcal pneumonia.

What does this patient need to know about their risk for heart disease and for the risk of malignancy?

  • Heart disease is more likely to occur in patients who have RA that is not effectively controlled due to ongoing inflammation. Clinicians should consider RA a risk factor for the development of cardiovascular disease.
  • Some studies to date have shown that RA patients on anti-TNF medications have a slightly higher risk for developing lymphoma. However, this is true of most medications used to treat RA and may indicate that it is the inflammation and not a particular drug which causes this. Patients may also have a slightly higher risk of non-melanoma skin cancers. In some studies this risk of malignancy did not appear to be statistically significant.

Patient Care

  1. Recognize the existence the 2010 Criteria for RA.
  2. Recognize the epidemiology of RA.
  3. Determine the most appropriate work up (serologic and radiographic testing) for a patient with polyarthritis.
  4. Recognize that smoking is a risk factor for more aggressive or treatment-resistant RA.
  5. Recognize the increased risk of cardiovascular disease in RA.
  6. Identify the need for PPD testing prior to initiating anti-TNF medications.

Medical Knowledge

  1. Recognize the differential diagnosis of polyarticular joint pain in an adult, and the most commonly involved joints in RA.
  2. Demonstrate how to test for an intra-articular effusion in the knee.
  3. Recognize that limitation in passive ROM represents intra-articular pathophysiology; active ROM extra-articular and differentiate between prepatellar bursitis and an intra-articular knee effusion.
  4. Distinguish between Swann-neck and Boutonniere's deformities.
  5. Describe the most common location for rheumatoid nodules and describe the histopathology of a nodule.
  6. Explain the significance of seropositivity as a risk for more aggressive disease and the significance of RF and CCP antibodies.
  7. Describe two extra-articular manifestations of RA (i.e., lung nodules, scleritis, episcleritis, amyloidosis).
  8. Locate and describe erosions on plain films of the hands.
  9. Identify the drugs most commonly used to treat RA and their main toxicities.

Interpersonal and communication skills

  1. Propose a standard of care treatment for a patient with newly diagnosed, erosive, seropositive RA.
  2. Summarize the common side effects of oral steroids for a patient who has never taken them.
  3. Recognize that NSAIDS and steroids are not appropriate monotherapy and contrast their use with the benefits of DMARDS for the patient.
  4. Discuss with a patient the factors that go into making the decision to replace a joint.

Professionalism

  1. Recognize the needs of a patient with a chronic disease and the effect on family and work performance.
  2. Understand the need to provide supportive, ongoing care.
  3. Describe the treatment issues of a young female who wants to become pregnant.
  4. Consent a patient for intra-articular steroid injection and discuss the indications for use.

Problem-based Learning

  1. Recognize that a normal ESR does not negate the findings of inflammation on exam.
  2. Explain how RF and CCP antibodies may impact on treatment decisions.
  3. Explain any hereditary factors and HLA associations involved in disease.
  4. Apply information about the joint exam and patient VAS to calculate a DAS 28.
  5. Apply information obtained on x-ray regarding disease severity to make decisions about appropriate care for the patient.

Systems Base Practice

  1. Implement a cost-effective therapy in a newly diagnosed RA patient.
  2. Demonstrate the ability to interact with physical and occupational therapists to enhance the care of patients with RA.
  3. Recognize the factors that lead to disability in patients with deforming RA.
  4. Incorporate considerations of cost and risk-to-benefit ratios in clinical evaluations, monitoring and therapeutic decisions, for the individual patient

Keywords: Rheumatoid Arthritis, Inflammatory Arthritis, Erosions, Rheumatoid Factor, Anti-CCP antibody

Key References